Treatment tailored to specific patient characteristics (i.e. personalized medicine) will have a significant positive impact on the delivery of healthcare. Personalized medicine for musculoskeletal pain conditions is a high priority because these conditions are a heavy burden to society due their economic impact and suffering they cause. Therefore, the ultimate goal of this line of research is to develop personalized interventions for musculoskeletal pain that ameliorate musculoskeletal pain and lessen their burden on society. We study shoulder pain because it is a common musculoskeletal pain condition and in the initial funding period we identified combinations of genetic and psychological risk factors indicative of chronic shoulder pain. In particular, a combination of COMT genetic variants and pain catastrophizing formed a high risk subgroup predictive of heightened shoulder pain responses in a pre-clinical exercise-induced injury cohort and poor 12 month outcomes in a clinical post-operative shoulder pain cohort. This promising and robust finding provided the impetus to transition this line of research to an intervention phase. The renewal application will provide resources for this multidisciplinary research team to determine mechanisms and efficacy of personalized pharmaceutical and psychological pain interventions designed to target genetic and psychological factors that comprise the high risk subgroup. The pharmaceutical intervention will be propranolol as it counters the effects of decreased COMT enzyme. The psychological intervention will be cognitive restructuring that lessen the impact of pain catastrophizing. Our primary hypothesis is that subjects receiving the combined personalized pharmaceutical and personalized psychological intervention will have decreased shoulder pain duration, peak pain intensity, and peak upper-extremity disability following exercise-induced shoulder injury, when compared to the combined placebo condition. In addition, we will investigate psychological, molecular, and pain sensitivity regulation as mechanisms of pain relief. Successful completion of the proposed study will have a strong impact on the field as it has the potential to alter standard of care by discovering effective personalized pain treatments for individuals that, without the treatments, would go on to develop chronic shoulder pain. Completion of this study will also provide critical foundational data for designing a subsequent clinical trial in a post-operative shoulder pain cohort.